The role of copper in liver disorders is best recognized in Wilson’s disease, in which hepatic copper accumulation is not only pathognomonic, but also pathogenic as a source of cellular reactive oxygen species.⁽¹⁾ Elevated hepatic copper is also found in cholestatic liver diseases, but this is likely a consequence of decreased biliary excretion of copper and not a cause of the underlying liver disease.^(2,3)

The opposite end of the spectrum (reduced hepatic copper concentration) is rarely reported in patients with liver diseases.⁽⁴⁾ In mammals, cytochrome-c oxidase, ceruloplasmin, hephaestin, and copper-zinc superoxide dismutase represent a partial list of cuproenzymes whose metabolism and function depend on copper availability.^(5-8)

In addition, copper plays a key role in the innate immune system, acting as a “bullet” for effective killing of bacteria and fungi by macrophages.⁽⁹⁾ Consequences of copper deficiency include iron overload, tissue fibrosis, cytopenia, and susceptibility to infections.^(10-14) Although these clinical features are also prevalent in advanced cirrhosis,^(15-17) the significance of copper deficiency in liver disorders has only been reported in human fatty liver disease and preclinical animal models.^(18-20)